Let Guinea Pigs be Guinea Pigs

Bioelectronic chips offer alternatives to lab animals

Lung-on-chip device (Emulate Inc.)

If you work in a biomedical research lab, you better not get emotionally attached to the lab animals. For some lab workers, it isn't easy. Those mice and guinea pigs, and sometimes rats, can look downright cute and cuddly. If, however, you can't jab the animals with compounds that make the critters sick, and even kill them, then you need to find a new line of work.

There's hope, however, for our furry friends from an emerging technology that can substitute small pieces of clear plastic that function like human organs, at least for some kinds of lab tests. Earlier in April, the U.S. Food and Drug Administration hired a Harvard University spin-off enterprise to find out if these organs-on-chips can indeed do the job.

Calling these simulated organs "chips" may be a misnomer. Like integrated circuits in computers, they perform designated functions and can be linked together as components in larger systems. But these miniature organ chips are more hand-held than "micro" in size, about the same dimensions as USB memory sticks. The devices are made from clear polymer plastic, with fine channels etched in the surface, or drilled through, which allow fluids in minute quantities to flow. Capillary action or tiny pumps move the fluids through the device.

The channels then are lined with human cells, which can be produced from stem cells if necessary. It's these human rather than animal cells that make organs-on-chips promising alternatives for lab testing. Different disease states or genetic disorders can be simulated on demand, with electronics to record and measure cellular activity attached to the chips, instead of interpreting the condition of lab animals.

Scientists use lab animals, of course, as substitutes or models for testing on humans. Small mammals like mice share many of the same biological functions, and even genetics, with humans. With the animals' shorter life spans, researchers can find out quickly how different compounds could work in the human body. Rodents like rats and mice can be bred to reflect specific human characteristics, such as a predisposition to specific diseases, and be induced to develop human disease conditions.

But there's another similarity with humans that makes testing difficult with lab animals, their complex genomics and protein chemistries. As a result, there's always a risk that test results with lab animals do not predict what happens in humans, which leads to erroneous conclusions. And those erroneous conclusions can have dire consequences. National Institutes of Health in 2012 cited data showing more than 30 percent of human clinical trials of new drugs fail because of toxic effects of those drugs on patients. And in many cases those toxic effects were not caught in earlier animal tests, one of the main reasons for testing with animals.

A better way to test for toxins

NIH, with FDA and Defense Advanced Research Projects Agency, began a project in 2012 to see if these chip devices can be a more reliable way than lab animals to test new drugs for toxicity. The initiative funded 10 studies focusing on research into cellular microsystems, and 7 inquiries into stem cells that transform into multiple cell types like the those found in organ tissue. These stem cells could act as a source of tissue cells to use in the devices.

One of the labs taking part in the project is the Wyss Institute for Biologically Inspired Engineering, a research center at Harvard University working on these devices. The Wyss Institute was already forging ahead with organs-on-chips, developing simulated organ and tissue devices, including those for the human heart, lung, airways, and gut. The lab also harnessed 3-D printing to make cardiac chip devices with built-in sensors, which speeds and simplifies production of the devices.

Wyss Institute is not the only facility at work with organs-on-chips. A joint biomedical engineering lab at University of North Carolina and North Carolina State are developing a miniaturized device, funded by NIH, derived from human stem cells to better simulate the workings of a human gut. And a team at University of California in Berkeley developed a device with cardiac tissue derived from stem cells to test drug candidates for potentially toxic effects, also as part of the 2012 NIH/FDA/Darpa project.

But Wyss Institute took the process one step further by spinning-off a private company to take these devices to market. Emulate Inc., located in Boston, was founded in 2014 by Donald Ingber, director of the Wyss Institute, and others to commercialize the lab's organ-on-chip discoveries. Ingber continues as chair of Emulate's scientific advisory board. The company raised $12 million in venture funding when it opened, and another $28 million in equity investment some two years later.

In the new project announced in April 2017, FDA and Emulate Inc. will evaluate organs-on-chips as direct replacements for lab animals to produce data for FDA's regulatory decisions. Emulate will develop chip devices simulating the livers in rats and dogs, as well as humans, and compare their functioning to tests with live animals and humans. The liver digests chemicals and filters out toxins from blood, thus its functions are critical in toxicity tests.

If successful, the project will help make it possible for FDA to accept drug toxicity tests from organ-on-chip devices instead of lab animals, which should spare at least a few lab animals from toxicity tests. But the chips will never be as cute as guinea pigs.

Alan Kotok is a Washington, DC-area writer and reporter, and editor and publisher of the daily news site Science & Enterprise. Kotok was previously managing editor of the careers section at Science magazine.